中文摘要：

目的 探讨基质金属蛋白酶-1 （MMP-1）和膜型1基质金属蛋白酶（MT1-MMP）在胆囊癌血管生成拟态中的表达及临床意义.方法 收集手术病理确诊的原发性胆囊癌74例和胆囊腺瘤、慢性胆囊炎各10例的石蜡标本及相关临床资料,应用免疫组化测定上述病变组织的MMP-1、MT1-MMP表达.应用Kaplan-Meier生存比较、Cox风险模型分析与胆囊癌血管生成拟态（VM）的相关性和临床意义.结果 ①胆囊癌MMP-1、MT1-MMP表达明显高于胆囊腺瘤、胆囊炎（P＜0.000 1）;VM（＋）胆囊癌MT1-MMP表达明显高于VM（-）胆囊癌（P=0.003 9）,而MMP-1则无差别.②MMP-1表达与VM（-）胆囊癌的Nevin分期（P=0.003 6）、分化程度（P=0.010）、肝转移（P=0.003）和淋巴结转移（P=0.002）正相关;MT1-MMP表达与VM（-）或VM（＋）胆囊癌的Nevin分期（P=0.013或P=0.033）、浸润深度（P=0.045或P=0.035）、淋巴结转移（P=0.046或P=0.025）和肝转移（P=0.030或P=0.027）正相关;MMP-1、MT1-MMP表达与VM（-）胆囊癌正相关.③VM（＋）胆囊癌MT1-MMP表达在Nevin S3-s5期（P =0.000 1）、侵犯浆膜（P=0.001）、淋巴结转移（P =0.000 2）和肝转移（P=0.004）同样分组条件下分别明显高于VM（-）胆囊癌;MMP-1仅在肝转移组,VM（＋）胆囊癌表达显著高于VM（-）（P=0.038）.④无论在MMP-1、MT1-MMP单独表达阳性或二者均阳性,VM（＋）胆囊癌患者术后5年生存期都明显短于VM（-）组（P=0.025 1或P=0.022 5或P=0.025 0）.Cox多因素分析表明,VM、浸润深度、淋巴结转移、肝转移、手术方式是影响胆囊癌患者预后的独立因素.结论 胆囊癌MMP-1、MT1-MMP高表达,MT1-MMP表达与胆囊癌VM相关,MMP-1则与胆囊癌VM无关.MMP-1,MT1-MMP可作为评判胆囊癌Nevin分期、浸润深度、淋巴结或肝转移及判断预后的重要指标;而MT1-MMP还可作为判断胆囊癌否存在VM和VM胆囊癌预后的重要指标.

英文摘要：

Objective To evaluate the expression of matrix metaUoproteinase-1 （ MMP-1 ） and membrane type-1matrix metalloproteinase （MT1-MMP） in human primary gallbladder carcinomas with vasculogenic mimicry （VM） and its clinical significance. Methods Seventy-four carcinomas, 10 adenomas and 10 chronic inflammatory lesions of the gallbladder underwent operation and histopathologically and their clinical-pathlogical confirmed data were studied and followedup. Immunohistochemistry （SABC） was used to determine the expression of MMP-1, MT1-MMP proteins in each paraffin section of every patient in vivo. Kaplan-Meier survival curves and Cox multiple factor were used to analyse the relation beteewn VM of gallbladder carcinomas and expression of MMP-1, MT1-MMP. Results （1） Expression of MMP-1 and MT1-MMP was increased significantly in carcinomas with or without VM than adenomas and inflammatory lesions of the gallbladder （P 〈 0.000 1 ） in. Eexpression of MT1-MMP in the gallbladder carcinomas with VM was increased significantly than that without VM〈 P = 0.003 9）, without difference on expression of MMP-1 between VM （ ＋ ） gallbladder carcinomas and VM （ - ） gallbladder carcinomas. （2） There is positive correlation between expression of MMP-1 and VM （ - ） gallbladder carcinomas in the cases of Nevin stage （P = 0.003 6）, differentiation degree （ P = 0. 010） ,liver metastatis （ P = 0. 003 ） and lymph node metastases （ P = 0.002 ）, the same correlation was observed between expression of MT1-MMP and VM （ ＋ ）/（ - ） gallbladder carcinomas in the cases of Nevin stage （P =0. 013 or P =0.003 3） ,invasion depth （P =0.045 or P =0. 035） ,lymph node metastases （P =0.046 or P =0.025 ） and liver metastatis （ P = 0. 030 or P = 0. 027 ） ; MMP-1 expression was positively correlated with MT1 -MMP expression in VM （ - ） gallbladder carcinomas. （3） Expression of MT1-MMP in the same conditions of Nevin stage （ S3 - S5, P = 0. 000 1 ）, serosal invasion （ P